Tang Liren, Dai Derek L, Su Mingwan, Martinka Magdalena, Li Gang, Zhou Youwen
Department of Dermatology and Skin Science , University of British Columbia, Vancouver, British Columbia, Canada.
Clin Cancer Res. 2006 Jun 15;12(12):3716-22. doi: 10.1158/1078-0432.CCR-06-0030.
The collagen triple helix repeat containing 1 (CTHRC1) is a promigratory protein first found to be expressed during rat tissue repair process. Recent preliminary results revealed CTHRC(1) mRNA in melanoma and breast cancer. However, the full significance of CTHRC1 to human carcinogenesis remains unclear. This study is to further characterize the clinical and functional relevance of CTHRC1 in melanoma and other human solid cancers.
First, semiquantitative immunohistochemistry analysis was done on 304 clinically annotated, paraffin-embedded biopsies representing different stages of melanoma progression. Then, short interfering RNA was used to inhibit expression of CTHRC1 protein for migration analysis on cultured melanoma cells. Finally, the CTHRC1 expression was surveyed in 310 samples representing 19 types of human solid cancers.
In benign nevi and noninvasive melanoma biopsies, there was little CTHRC1 protein expression. In contrast, in invasive primary melanomas, there was a significant increase of CTHRC1 protein (P < 0.01, chi(2) test). There was a further increase of CTHRC1 protein in metastatic melanoma specimens compared with nonmetastatic lesions (P < 0.01, chi(2) test). In addition, inhibition of CTHRC1 expression resulted in decreased cell migration in vitro. Finally, transcription survey in 19 types of human solid cancers revealed aberrant CTHRC1 expression in 16 cancer types, especially cancers of the gastrointestinal tract, lung, breast, thyroid, ovarian, cervix, liver, and the pancreas.
Aberrant expression of CTHRC1 is widely present in human solid cancers and seems to be associated with cancer tissue invasion and metastasis. It potentially plays important functional roles in cancer progression, perhaps by increasing cancer cell migration.
含1型胶原三螺旋重复序列蛋白（CTHRC1）是一种促迁移蛋白，最初发现其在大鼠组织修复过程中表达。近期初步研究结果显示黑色素瘤和乳腺癌中存在CTHRC1 mRNA。然而，CTHRC1对人类致癌作用的全部意义仍不明确。本研究旨在进一步明确CTHRC1在黑色素瘤及其他人类实体癌中的临床及功能相关性。
首先，对304份代表黑色素瘤进展不同阶段的经临床注释的石蜡包埋活检组织进行半定量免疫组化分析。然后，使用小干扰RNA抑制CTHRC1蛋白表达，对培养的黑色素瘤细胞进行迁移分析。最后，在代表19种人类实体癌的310份样本中检测CTHRC1表达情况。
在良性痣和非侵袭性黑色素瘤活检组织中，CTHRC1蛋白表达很少。相比之下，在侵袭性原发性黑色素瘤中，CTHRC1蛋白显著增加（P < 0.01，卡方检验）。与非转移性病变相比，转移性黑色素瘤标本中CTHRC1蛋白进一步增加（P < 0.01，卡方检验）。此外，抑制CTHRC1表达导致体外细胞迁移减少。最后，对19种人类实体癌的转录研究显示，16种癌症类型中存在CTHRC1异常表达，尤其是胃肠道、肺、乳腺、甲状腺、卵巢、宫颈、肝脏和胰腺的癌症。
CTHRC1异常表达广泛存在于人类实体癌中，似乎与癌组织侵袭和转移有关。它可能在癌症进展中发挥重要功能作用，或许是通过增加癌细胞迁移来实现。
